PROJECT SUMMARY/ABSTRACT: OVERALL The Minnesota HHEAR Targeted Analysis Laboratory brings together investigators from the University of Minnesota and the Minnesota Department of Health with broad and internationally recognized expertise in the identification and analysis of agents that are potentially harmful to human health at all ages. The combination of expertises in our proposed laboratory is unique. Our scientists have years of experience in the development and application of state-of-the-art high throughput analytical chemistry methods based mainly on mass spectrometry for the assessment of trace amounts of targeted toxicant or carcinogen metabolites in large clinical and epidemiological studies. Our scientists also have developed and applied methods for the analysis of DNA adducts of cancer-causing agents in human samples. There are few groups that can bring together a team with such superb and creative expertise on multiple relevant levels of exposure assessment. Therefore, our overall goal is to provide human health researchers with access to state-of-the-art infrastructure for targeted analysis of biological samples. We see this goal as firmly embedded within the concept of the exposome and its relationship to human health. The specific aims of each component resource and the development core are as follows. The Targeted Analysis Resource will use predominantly high throughput mass spectrometric methods with well-established quality control procedures to provide timely and reliable quantitative data relevant to 3 major areas of importance to human health: Exposure to tobacco-specific compounds; exposure to environmental, lifestyle, and nutritional toxicants and carcinogens; and variations in levels of endogenous electrophiles and dietary compounds. The Developmental Core will establish new high throughput methods to measure multiple classes of toxicants and biomarkers in urine, plasma, hair, and toenails; to detect nutritional biomarkers from the intake of foods and beverages in urine and plasma; to develop assays to detect a panel of internal biomarkers of stress in multiple biospecimens; and expand our approaches to detect DNA adducts in saliva, blood and formalin-fixed tissues. The Administrative Core will coordinate all activities within the Minnesota HHEAR Targeted Analysis Laboratory. In addition, this core will be the primary link to the HHEAR Coordinating and Data Centers as well as the HHEAR investigators at all stages of their projects. Collectively, the Minnesota HHEAR Targeted Analysis Laboratory will contribute to a productive and effective HHEAR network designed to understand the impact of environmental exposures on human health.